Molecular mechanisms of the onset of major depressive disorder by regulating both phosphorylation and protein methylation in the white matter of brain

2015 Fiscal Year Final Research Report

• Project/Area Number: 25430079
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: Kinki University
• Principal Investigator: MIYATA Shingo 近畿大学, 東洋医学研究所, 准教授 (70403194)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: うつ病 / 脳白質 / 髄鞘 / オリゴデンドロサイト / 慢性ストレス / リン酸化 / タンパクメチル化

Outline of Final Research Achievements

Although dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis by chronic stress is indicative of major depression, the molecular mechanisms and functional changes in the brain underlying depression are largely unknown. In this study, by using chronic stress for mice, we attempted to elucidate the molecular pathway induced by elevated plasma corticosterone levels. We observed the following effects both, in vivo and in vitro: (1) repeated exposure to stress activates the 3-phosphoinositide-dependent protein kinase (PDK1)-serum glucocorticoid regulated kinase (SGK1)-N-myc downstream-regulated gene 1 (NDRG1)-adhesion molecule stabilization pathway via an increase in plasma corticosterone levels; and (2) the activation of this signaling pathway induces morphological changes in oligodendrocytes. Our data strongly suggest that these abnornalities of oligodendrocytes are possibly related to depression-like symptoms.

Free Research Field

神経化学